Evidence-Based Reviews

Atypical antipsychotics for delirium: A reasonable alternative to haloperidol?

Current Psychiatry. 2011 January;10(1):37-46

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Although we used this evidence, in part, to select an atypical antipsychotic for Ms. B, this model should be used only to estimate the possible anticholinergic burden associated with a specific medication or combination. The risk of anticholinergic burden needs to be considered along with a medication’s potential nonanticholinergic adverse effects and the patient’s overall clinical history (eg, past sensitivity to anticholinergic agents, memory complaints, effectiveness of an agent, concomitant medications, disease state, adherence concerns). For example, an atypical antipsychotic that is potently anti-histaminergic and therefore sedating could be beneficial when treating an agitated delirium patient. Establishing the presence of a risk of anticholinergic burden cannot be equated with the presence of anticholinergic toxicity, because the exact relationship between AA and cognitive performance is still unknown.^32,33

Cardiovascular safety

Clinical Point

Haloperidol increases QTc interval and may increase risk of ventricular dysrhythmia and sudden cardiac death

The most common cardiovascular effects of atypical antipsychotics are tachycardia, hypotension (usually mild), and prolongation of QTc interval.³⁴ For example, haloperidol, 15 mg/d, was found to increase mean QTc by 7 msec, with a reported odds ratio ranging from 2.2 to 6.1 for ventricular dysrhythmia and sudden cardiac death,³⁵ although risk may be more strongly associated with high-dose, IV haloperidol.³⁶

QTc interval prolongation warrants concern because it suggests that patients may be predisposed to torsades de pointes (TdP). Conventional antipsychotics— especially phenothiazines—have the highest risk of inducing TdP. One review concluded that compared with other antipsychotics, chlorpromazine, pimozide, thioridazine, and the atypical clozapine have a higher risk of cardiac arrhythmias and sudden cardiac death.¹¹ Another review found cases of TdP with haloperidol, ziprasidone, olanzapine, and thioridazine.³⁷ When prescribing an antipsychotic, consider both pharmacologic and nonpharmacologic risks factors, including preexisting cardiovascular disease, female sex, hepatic insufficiency, electrolyte abnormalities, stimulant drug abuse,³⁶ and genetic predisposition (Table 6).^11,35-37

Table 6

Risk factors for antipsychotic-induced QT interval prolongation and torsades de pointes*

Pharmacologic
Antipsychotic selection
Drug interaction (QT-prolonging agents)
Drug interaction (slow metabolism by cytochrome P450 inhibitors of 2D6, 3A4, 1A2)
Nonpharmacologic
Advanced age (>65)
Bradycardia
Hypokalemia
Hypomagnesemia
Hepatic/renal dysfunction
Genetic predisposition
Female sex
Screening (major risk factors)
Structural cardiac disease
Congenital long QT syndrome
Family history of sudden cardiac death
Previous episodes of drug-induced QT prolongation or torsades de pointes
* Serial electrocardiograms are recommended for patients with a major risk factor or multiple pharmacologic/ nonpharmacologic risk factors Source: References 11,35-37

Related Resource

Stern TA, Celano CM, Gross AF, et al. The assessment and management of agitation and delirium in the general hospital. Prim Care Companion J Clin Psychiatry 2010;12(1):e1–e11. www.psychiatrist.com/private/pccpdf/article_wrapper.asp?art=2010/09r00938yel/09r00938yel.htm.

Drug Brand Names

Amitriptyline • Elavil
Aripiprazole • Abilify
Atropine • Sal-Tropine
Chlorpromazine • Thorazine
Clozapine • Clozaril
Diphenhydramine • Benadryl
Haloperidol • Haldol
Nortriptyline • Aventyl
Olanzapine • Zyprexa
Pimozide • Orap
Quetiapine • Seroquel
Risperidone • Risperdal
Thioridazine • Mellaril
Ziprasidone • Geodon

Disclosures

Dr. Spiegel is a speaker for AstraZeneca, Pfizer, Inc., and Janssen Pharmaceuticals.

Drs. Ahlers, Yoder, and Qureshi report no financial relationship with any company whose products are mention in this article or with manufacturers of competing products.